Amgen: EC approves IMDYLLTRA (tarlatamab) for ES‑SCLC after platinum therapy
- European Commission authorises IMDYLLTRA (tarlatamab) as monotherapy for adults with extensive‑stage small cell lung cancer after progression on or after first‑line platinum‑based chemotherapy.
- DeLLphi‑304 randomised 509 patients and showed a 40% reduction in risk of death with tarlatamab versus chemotherapy (median OS 13.6 vs 8.3 months; HR 0.60; 95% CI 0.47–0.77; P<0.001).
- Key safety signals include cytokine release syndrome in 56.7% of patients (serious CRS 19.7%), with CRS occurring mainly after the first two doses and requiring in‑facility monitoring.
- EU dosing is step‑up: 1 mg Day 1 then 10 mg Day 8, Day 15 and every two weeks; monitor 6–8 hours on Cycle 1 Day 1 and Day 8 and advise caregiver proximity for 24 hours after those infusions.
Regulatory decision
The European Commission granted marketing authorisation for IMDYLLTRA (tarlatamab) as a monotherapy to treat adults with extensive‑stage small cell lung cancer who require systemic therapy following disease progression on or after first‑line platinum‑based chemotherapy.
Phase 3 DeLLphi‑304 results
DeLLphi‑304 was a global, randomised, controlled, open‑label Phase 3 trial that randomised 509 patients to tarlatamab or local standard‑of‑care chemotherapy. The trial demonstrated a statistically significant overall survival benefit: tarlatamab reduced the risk of death by 40% and extended median overall survival to 13.6 months versus 8.3 months with chemotherapy (hazard ratio 0.60; 95% CI 0.47–0.77; P < 0.001). Results were presented at ASCO 2025 and published in The New England Journal of Medicine.
Safety and administration
The safety profile was consistent with prior data. The most common adverse reactions included cytokine release syndrome (CRS) (56.7%; serious CRS 19.7%), decreased appetite, pyrexia, dysgeusia, constipation, anaemia and fatigue; CRS primarily occurred after the first two doses. Under the EU Summary of Product Characteristics, the recommended dosing is a step‑up schedule—1 mg on Day 1 followed by 10 mg on Days 8 and 15 and then every two weeks—and patients should be monitored from the start of infusion for 6 to 8 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting, with caregiver proximity advised for 24 hours after those infusions.
Ongoing development
Tarlatamab continues to be evaluated across the DeLLphi programme in multiple Phase 1b, Phase 2 and Phase 3 studies testing combinations, alternative dosing strategies, subcutaneous administration and use in earlier lines and stages of SCLC.
Source: Amgen
